Preethy Senthilkumar, Sakamoto Shuji, Higuchi Takuma, Ichiyama Koji, Yamamoto Naoki, Ikewaki Nobunao, Iwasaki Masaru, Dedeepiya Vidyasagar Devaprasad, Srinivasan Subramaniam, Raghavan Kadalraja, Rajmohan Mathaiyan, Senthilkumar Rajappa, Abraham Samuel Jk
Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India.
Laboratory of Molecular Biology, Science Research Center, Kochi University, Nankoku, Japan.
Sci Rep. 2025 Feb 28;15(1):7232. doi: 10.1038/s41598-025-92258-4.
Duchenne muscular dystrophy (DMD) is a rare genetic disease, causing muscle degeneration due to lack of dystrophin with inadequate muscle regeneration culminating in muscle dysfunction. The N-163 strain of Aureobasidium Pullulans produced Beta-1,3 - 1,6-glucan (Neu REFIX) reported to be safe with anti-inflammatory and anti-fibrotic efficacy earlier, herein we evaluated its effects on muscle regeneration in mdx mice. Forty-five mice in three groups (n = 15 each): Group 1 (normal), Group 2 (mdx control), and Group 3 (mdx fed Neu REFIX) were evaluated for 45 days. IGF-1, Dystrophin, CD44 and MYH3 in diaphragm, plasma and skeletal muscle were evaluated by ELISA and immunohistochemistry. Mean IGF-1 expression was 20.32% and 16.27% higher in plasma (p = 0.03) and diaphragm respectively in Neu-REFIX group. Mean dystrophin was higher in Neu-REFIX group by 70.3% and 4.7% in diaphragm and plasma respectively than control. H-score intensity of CD44 + was > 2.0 with an MYH3-positivity 20% higher in Neu-REFIX than control. Oral administration of Neu REFIX was safe. Significantly enhanced plasma IGF-1 beside increased Dystrophin, MYH3 and CD44, proving a restoration of muscle regeneration and differentiation, especially in diaphragm, makes us recommend it as a disease modifying adjuvant in both early and advanced stages of DMD.
杜氏肌营养不良症(DMD)是一种罕见的遗传性疾病,由于缺乏肌营养不良蛋白导致肌肉退化,肌肉再生不足,最终导致肌肉功能障碍。前期报道指出,出芽短梗霉N-163菌株产生的β-1,3-1,6-葡聚糖(Neu REFIX)具有安全性,且具备抗炎和抗纤维化功效。在此,我们评估了其对mdx小鼠肌肉再生的影响。将45只小鼠分为三组(每组n = 15只):第1组(正常组)、第2组(mdx对照组)和第3组(mdx喂养Neu REFIX组),评估期为45天。通过酶联免疫吸附测定(ELISA)和免疫组织化学法评估膈肌、血浆和骨骼肌中的胰岛素样生长因子-1(IGF-1)、肌营养不良蛋白、CD44和肌球蛋白重链3(MYH3)。Neu-REFIX组血浆中IGF-1的平均表达分别比对照组高20.32%和膈肌中高16.27%(p = 0.03)。Neu-REFIX组膈肌和血浆中的肌营养不良蛋白平均分别比对照组高70.3%和4.7%。CD44 +的H评分强度>2.0,Neu-REFIX组中MYH3阳性率比对照组高20%。口服Neu REFIX是安全的。除了增加肌营养不良蛋白、MYH3和CD44外,血浆IGF-1显著增强,证明肌肉再生和分化得到恢复,尤其是在膈肌中,这使我们推荐它作为DMD早期和晚期的疾病修饰辅助药物。